Methods for Injecting Samples in Liquid Chromatography, Particularly in High Performance Liquid Chromatography

ABSTRACT

A sample injection method for liquid chromatography is performed with an injection valve having a waste port, two sample loop ports, and two high-pressure ports. One high-pressure port can be connected to a pump and the other high-pressure port can be connected to a chromatography column. A sample loop is connected to one of the sample loop ports on one end and to a pump volume of a sample conveying device on the other end. A section of the sample loop can be separated to facilitate receiving a sample fluid in the sample loop. A control unit controls the injection valve and the sample conveying device. The sample injector allows a sample to be loaded into the sample loop and then pressurized to an operating pressure prior to injecting the sample into the chromatography column. The sample loop may also be isolated from the operating pressure for facilitating depressurization of the loop.

CROSS-REFERENCE TO RELATED APPLICATION

Applicant claims the benefit, under 35 U.S.C. §120, of U.S. patentapplication Ser. No. 12/863,976 filed Jul. 21, 2010, and entitled“Sample Injector for Liquid Chromatography, Particularly for HighPerformance Liquid Chromatography.” The entire content of this priorpatent application is incorporated herein by this reference.

TECHNICAL FIELD OF THE INVENTION

The invention pertains to methods for injecting samples for liquidchromatography, particularly for high performance liquid chromatography(HPLC). The sample injection process provides for pressure compensationduring a sample injection sequence, or during a post sample injectionsequence, or during both sequences.

BACKGROUND OF THE INVENTION

In HPLC, a sample to be examined needs to be injected into ahigh-pressure fluid flow, wherein this flow can be interrupted only asbriefly as possible. For this purpose, high-pressure injection valvesare used that allow a nearly uninterrupted change-over of the fluidflow. Such a design is described, for example, in U.S. Pat. No.3,530,721. This patent was derived from an original application that waspublished in 1965.

U.S. Pat. No. 4,939,943 discloses a sample injector with a “highpressure syringe unit.” The basic Split Loop Principle of the sampleinjector disclosed in this application has proven effective in HPLC.

Furthermore, WO 2006/083776 discloses a sample injector for preventingpressure surges that occur during the actuation of the high-pressurevalve and could negatively affect the efficiency and the service life ofthe chromatography column.

During the actuation of the injection valve, compression anddecompression volumes flow through the valve with high speeds. Accordingto non-previously-published German Patent Application DE 10 2007 059 651A1 of the applicant of Dec. 10, 2007, which pertains to a sampleinjector for high performance liquid chromatography and features ahigh-pressure change-over valve with optimized service life, these flowscause damage to the high-pressure valve components.

The service life of the high-pressure change-over valve determines theoperating costs of an HPLC system. These costs should be maintained aslow as possible by minimizing the wear of the high-pressure valvecomponents.

SUMMARY OF THE INVENTION

The invention includes a sample injector for liquid chromatography,particularly for high performance liquid chromatography, in which theinjection valve also has an improved service life under extremely highpressures.

Embodiments of the invention apply the Split Loop Principle for a sampleinjector to facilitate a pressure compensation when the switchingpositions of the injection valve are changed. The pressure compensationis made possible by an injection valve which features a PRESSURECOMPENSATION position, in which the sample loop ports of the injectionvalve connected to the ends of the sample loop are not connected toother ports in the injection valve.

In the Split Loop Principle, the sample loop is divided in theconnecting piece between the sample conveying device that may berealized, for example, in the form of a syringe and the respectivesample loop port of the injection valve. In order to take in therequired sample volume or to take in a flushing medium, the end of theintake segment of the separated connecting piece of the sample loop thatis connected to the sample conveying device is moved to a samplecontainer or a container for a flushing medium. Subsequently, thedivided connecting piece of the sample loop is reconnected such that thesample volume can be injected into the chromatography column by means ofthe pump in the INJECT position of the injection valve. This basicprinciple is already described in U.S. Pat. No. 4,939,943. In this case,the special Split Loop Principle provides the advantage that the sampleconveying device is flushed with eluent after the injection of thesample such that it is normally not required to flush the sampleconveying device, the sample loop and the injection valve after theinjection of a sample.

After taking in the sample volume in the LOAD position, the injectionvalve is, according to one or more embodiments of the invention, changedover into the PRESSURE COMPENSATION position, in which the sample loopports are shut in a pressure-tight fashion. In this position, the driveof the sample conveying device is controlled in such a way that pressurebuilds up in the closed sample loop and in the pump volume of the sampleconveying device, wherein this pressure essentially corresponds to thepressure with which the pump feeds the fluid to the chromatographycolumn in the LOAD position or in the INJECT position. Even if thepressure in the sample loop is not identical to the pressure of the pumpbefore the injection valve is changed over from the PRESSURECOMPENSATION position into the INJECT position and a slight differentialpressure remains, this slight differential pressure is, according to theinvention, maintained so low that it can neither disadvantageouslyeffect the flow through the chromatography column nor cause damage tothe injection valve or the chromatography column.

This applies analogously to the change-over from the INJECT positioninto the LOAD position. In this case, the valve also is initiallychanged over from the INJECT position into the PRESSURE COMPENSATIONposition, in which the pressure that essentially corresponds to the pumppressure is reduced until essentially the ambient pressure is reached.If applicable, a slight, harmless differential pressure may also remainin this case when the valve is changed over from the PRESSURECOMPENSATION into the LOAD position.

According to the invention, the pressure compensation (pressure increaseor pressure reduction) in the sample loop is achieved by controlling thedrive of the sample conveying device accordingly.

In contrast to prior sample injectors, the fluid flows created duringthe pressure compensation no longer flow through the change-over valvesuch that damage to valve components due to excessively high flow speedscan no longer occur.

Naturally, this objective also is at least partially attained if thepressure compensation is only carried out in one of the two change-overdirections described above.

According to one preferred embodiment of the invention, the twohigh-pressure ports are connected in the PRESSURE COMPENSATION positionof the injection valve. Due to this measure, the flow of the fluidthrough the chromatography column is maintained and no undesirable peakscan occur in the progression of pressure during the change-overprocesses.

According to one embodiment of the invention, the injection valvefeatures a rotor and a stator, wherein the rotor features a face thatcooperates with the face of the stator and contains at least threegrooves that either connect or shut port opening cross sections of thehigh-pressure ports, the sample loop ports and the waste port arrangedin the face of the stator in a pressure-tight fashion as a function ofthe rotational position of the rotor relative to the stator. The groovethat connects the two high-pressure ports in the LOAD position of theinjection valve is realized so long that it still connects thehigh-pressure ports after the stator and the rotor are turned into thePRESSURE COMPENSATION position. This groove therefore is elongated incomparison with the corresponding groove of conventional injectionvalves.

According to the preferred field of application of the invention, namelyin HPLC, the sample conveying device is realized in ahigh-pressure-resistant fashion and can generate the pressures used inHPLC, preferably pressures greater than 500-600 bar, particularlypressures greater than 1000 bar.

The sample conveying device may feature a movable element that is guidedin a pump volume in a sealed fashion and can be moved by means of adrive of the sample conveying device that is controlled by the controlunit in order to convey the fluid contained in the pump volume. Thesample conveying device may, in particular, be realized in the form of asyringe that is driven by means of a drive, wherein the movable elementis formed by the plunger of the syringe.

The control unit can move the plunger or the movable element by apredetermined distance after the PRESSURE COMPENSATION position of theinjection valve is reached by controlling the drive accordingly, whereinthis predetermined distance suffices for realizing a change of the pumpvolume of the sample conveying device required due to the elasticitiesof the devices conveying the fluid and the compressibility of the fluiditself such that a pressure reduction in the sample loop to essentiallythe ambient pressure can be achieved by increasing the pump volume and apressure increase in the sample loop to essentially the operatingpressure of the pump can be achieved by decreasing the pump volume. Themovement of the movable element may take place in a controlled orregulated fashion.

In order to allow a control of the pressure or the ultimate pressureduring the pressure compensation in the sample loop, a sensor may beprovided that measures the pressure of the fluid in the closed sampleloop or in the pump volume of the sample conveying device at least whilethe injection valve is in the PRESSURE COMPENSATION position.

In this variation, the signal of the pressure sensor is preferably fedto the control unit, wherein the control unit compares the pressure ofthe fluid with a nominal pressure value and controls the sampleconveying device in such a way that the pressure of the fluid reaches anominal high-pressure value before the injection valve is changed overfrom the PRESSURE COMPENSATION position into the INJECT position and/orthat the pressure of the fluid reaches a nominal low-pressure valuebefore the injection valve is changed over from the PRESSURECOMPENSATION position into the LOAD position.

These and other advantages and features of the invention will beapparent from the following description of the preferred embodiments,considered along with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is described in greater detail below with reference to thedrawings. In these drawings:

FIG. 1 shows a schematic representation of an HPLC system with a sampleinjector according to the invention, to which a chromatography column isconnected, wherein the injection valve is situated in the LOAD positionand the process of taking in a sample volume can begin in the stateshown;

FIG. 2 shows the HPLC system of FIG. 1, wherein the plunger of thesyringe was moved into the end position (position C) in order to take inthe sample volume;

FIG. 3 shows the HPLC system of FIG. 2, wherein the sample needle wasmoved into the injection port;

FIG. 4 shows the HPLC system of FIG. 3, wherein the injection valve waschanged over from the LOAD position into the PRESSURE COMPENSATIONposition;

FIG. 5 shows the HPLC system of FIG. 4, wherein the plunger was movedinto the position B in order to realize a pressure compensation(pressure increase) in the sample loop;

FIG. 6 shows the HPLC system of FIG. 5, wherein the injection valve waschanged over from the PRESSURE COMPENSATION position into the INJECTposition;

FIG. 7 shows the HPLC system of FIG. 6, wherein the injection valve waschanged over from the INJECT position into the PRESSURE COMPENSATIONposition after the injection of the sample volume;

FIG. 8 shows the HPLC system of FIG. 7, wherein the plunger was movedinto the end position (position C) in order to realize a pressurecompensation (pressure reduction), and

FIG. 9 shows the HPLC system of FIG. 8, wherein the injection valve waschanged over from the PRESSURE COMPENSATION position into the LOADposition.

DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

FIG. 1 shows a schematic representation of an HPLC system with a sampleinjector 10 that operates in accordance with the Split Loop Principleand features a sample conveying device 5, an injection valve 3 and ahigh-pressure pump 40. The sample injector 10 furthermore features asample loop that includes a first connecting piece 51 and a secondconnecting piece 52, 44. These may be comprised of a pressure-resistantline with a small diameter, for example in the form of a capillary tubeof glass or stainless steel. The connecting piece 51 is connected to afirst sample loop port 16 of the injection valve 3 and to the sampleconveying device or its pump volume V, respectively. The secondconnecting piece is comprised of an intake segment 44 and a feed segment52 and is realized in a separable fashion. For this purpose, the feedsegment 52 leads into an injection port 45 that is connected to a secondsample loop port 13 of the injection valve 3 via the feed segment 52.The intake segment 44 that is connected to the pump volume V of thesample conveying device 5 with one end features on its other end asample needle 42, by means of which the intake segment 44 can beconnected to the injection port 45.

However, the sample needle 42 can also be moved to a sample container 43and take in a defined sample volume into the intake segment 44 asdescribed in greater detail below. Furthermore, the sample needle 42 canalso be moved to a (not-shown) container for a flushing fluid in orderto withdraw flushing fluid for a flushing process and to clean thesample loop 51, 52, 44, the pump volume V and, if applicable, also theports and the grooves or channels of the injection valve. Due to thespecial topology of the Split Loop Principle shown, flushing of thesample loop 51, 52, 44 and of the sample conveying device 5 is normallynot required because they are flushed during an injection processanyway, namely with eluent supplied by the pump 40. However, the outsideof the sample needle 42 can also be cleaned by immersing the needle intoa container with cleaning or flushing fluid.

In the embodiment shown, the sample conveying device 5 comprises asyringe 50, in which a plunger 53 is guided in a displaceable andpressure-tight fashion. The plunger 53 is driven by means of a drive 55that is realized, for example, in the form of a stepping motor. Thedrive 55 is controlled by a control unit 60. The control unit 60 alsocontrols the change-over processes of the injection valve 3 thatfeatures a not-shown controllable drive.

A waste port 12 of the injection valve is connected to a waste line 47,from which fluid can be discharged into a not-shown waste reservoir.

The high-pressure pump 40 is connected to a high-pressure port 15 of theinjection valve. A chromatography column 41 is connected to the otherhigh-pressure port 14. The high-pressure pump 40 may be integrated intoand form part of the sample injector or be arranged in another unit or aseparate pump unit.

The injection valve 3 includes a stator 1 and a rotor 2. The stator 1features the two high-pressure ports 14, 15, the two sample loop ports13, 16 and the waste port 12. The injection valve 3 is connected to theother functional elements of the HPLC system via these ports and theabove-described connecting lines that may be realized in the form ofcapillary connections. The high-pressure screw connections required forthis purpose are not illustrated in FIG. 1 in order to provide a betteroverview. For reasons of simplicity, the injection valve is illustratedin the interface between the stator 1 and the rotor 2, wherein thedesign of the face of the stator 1 and the design of the face of therotor 2 are shown in order to better comprehend the function of theinjection valve. Within the injection valve 3, the ports are realized inthe form of bores that lead to the other side of the stator 1. The rotor2 features a number of arc-shaped grooves 21, 23, 25 that are exactlyaligned with the bores of the input and output ports.

The rotor 2 is pressed against the stator with a certain pressing forcesuch that a common interface between the rotor 1 and the stator 2 isformed, at which both components are mutually sealed. In this case, thepressing force is chosen so high that the arrangement also remainssealed at the highest pressures to be expected.

In the first LOAD position of the valve 3 illustrated in FIG. 1, thegrooves 21, 23, 25 are aligned relative to the ports 12-16 in such a waythat the grooves 23 and 25 respectively connect the two high-pressureports 14, 15 and the waste port 12 to the sample loop port 13. In thisLOAD position, the high-pressure pump 40 therefore conveys fluid in thedirection of the chromatography column 41. Furthermore, the sample loopport 16 is closed in a pressure-tight fashion.

In the state illustrated in FIG. 1, the sample needle 42 is moved intothe sample container 43 such that a sample volume can be taken in. Forthis purpose, the plunger 53 is situated in the position A and can bemoved into the position C by the control unit 60 in order to take in thesample volume. The desired defined sample volume is then withdrawn intothe intake segment 44, wherein the volume of the sample is smaller thanthe volume of the intake segment 44 such that the sample fluid cannotmix with the fluid supplied by the high-pressure pump in the pumpvolume. FIG. 2 shows the state of the HPLC system after the intakeprocess is completed.

In order to inject the sample volume situated in the intake segment 44,the sample needle 42 is moved into the injection port 45. This portseals the needle point in a high-pressure-resistant fashion. This stateis illustrated in FIG. 3.

In the next step, the pressure in the sample loop is adjusted to theoperating pressure of the chromatography column 41, i.e., to thepressure, with which the high-pressure pump 40 supplies fluid to theinlet of the chromatography column 41. For this purpose, the injectionvalve is initially changed over into a PRESSURE COMPENSATION position,in which the connecting piece 51 and the second connecting piece or thefeed segment 52 of the sample loop are not connected to the othercomponents connected to the injection valve 3 (FIG. 4).

In this PRESSURE COMPENSATION position, the plunger 53 of thehigh-pressure-resistant sample conveying device is moved into theposition B (FIG. 5). In order to prevent an interruption of the flowthrough the chromatography column 41 while conveying the volume requiredfor the compression of the sample loop content, the groove 25 in therotor 2 of the valve is realized in a correspondingly elongated fashionsuch that the two high-pressure ports 14, 15 are still connected in thePRESSURE COMPENSATION position. The travel of the plunger 53 fromposition C into position B required for building up the pressure can becalculated from the compressibility of the fluid volume enclosed in thesample conveying device 5 and in the sample loop, the elasticity of thearrangement and the current pump pressure. Alternatively, a pressurecompensation can be achieved with the aid of a control circuit for thepressure in the high-pressure-resistant sample conveying device. Forthis purpose, the pressure needs to be measured at a suitable locationand the position of the plunger 53 in the sample conveying device 5needs to be adjusted by the drive 55 in such a way that the pressurecorresponds to the required target pressure (=column pressure). Pressuremeasurement may be realized with a pressure sensor such as sensor 56 orindirectly by means of a force measurement. Conceivable solutions areforce measurements on the plunger 53 or in the drive 55. After pressureequality is achieved, the valve is changed over into the INJECT positionin order to inject the sample volume into the column 41 (FIG. 6).

In the embodiment shown, the control unit 60 measures the force that thedrive 55 needs to exert in order to achieve a corresponding compressionin the sample loop. For this purpose, the drive 55 may feature anintegrated sensor 57, the signal of which is fed to the control unit 60(as indicated with a double arrow between the drive 55 and the controlunit 60). Due to this measure, the control unit can determine the actualpressure in the pump volume and therefore in the sample loop (thepressure drop in the connecting pieces and in the valve is negligiblysmall) and adjust this pressure to the desired value.

After the entire sample volume has been conveyed from the intake segment44 to the column 41 by means of the fluid conveyed by the pump 40, thevalve can be once again changed over into the PRESSURE COMPENSATIONposition in order to decompress the sample loop (FIG. 7).

The plunger 53 is moved from the position illustrated in FIG. 7 intoposition C. This causes the pressure in the sample loop to be adjustedto the atmospheric pressure. This state of the HPLC system isillustrated in FIG. 8. During this decompression time in the PRESSURECOMPENSATION position of the injection valve 3, the column 41 is alreadyconnected to the pump 40 via the elongated groove 25 in order to preventpressure drops. The travel of the plunger 53 from position B to positionC can either be calculated analogous to the compression in FIG. 5 ordetermined by measuring and controlling the pressure. Alternatively, thepressure can also be determined indirectly by means of a forcemeasurement on the plunger 53 or on the drive 55 of the plunger.

After the sample loop has been decompressed, the valve 3 is changed overinto the LOAD position (FIG. 9). No damaging flows in the injectionvalve occur during this process.

The plunger 53 of the high-pressure-resistant sample conveying device 5can now be moved back into the starting position A. The excess quantityof fluid is discharged via the waste connection 47. The unpressurizedneedle 42 can subsequently be moved from the needle seat of theinjection port 45 to the corresponding sample container 43 in order totake in the next sample.

The position C during the decompression may also differ from thestarting position A prior to the compression. For example, if gradients(time-controlled mixing ratio of the eluent) are pumped through thecolumn, the position C at the end of the decompression may differbecause the compressibility of the loop content may have changed.

The control unit 60 can store predetermined positions A, B, C and/ordifferences in the distance between these positions as a function ofparameters of the entire sample injector, particularly thecompressibility of the eluent, elasticity properties of the sample loopand the sample conveying device, etc. The plunger can then beautomatically moved into these positions (i.e., without a control) orthese positions may serve as approximate values or initial values for acontrolled movement.

In order to determine the positions A, B, C and the respective travel ofthe plunger, a change-over of the injection valve 3 may be carried outwithout compression or decompression, respectively. The pressure dropcan then be determined by means of a pressure sensor and the requiredtravel as well as the respective positions B or C can be determinedbased on this pressure drop. The thusly determined values can then bestored and used for other change-over processes, in which a compressionor decompression takes place. A corresponding sensor may also beprovided in the pump 40. Pumps of this type for HPLC always feature apressure sensor for controlling the conveyed eluent anyway. Thecompressibility of the medium, particularly of the eluent, can also bedetermined by means of the pump 40. Such pumps are realized, forexample, in the form of dual-plunger pumps, in which the change-overfrom one plunger to the other plunger is suitably controlled orregulated by means of a pressure sensor and a control unit in such a waythat a highly constant flow rate is achieved. Since the compressibilityof the medium also needs to be taken into account during thischange-over process, the compressibility can be determined by suitablycontrolling the dual-plunger pump during the change-over from oneplunger to the other plunger and fed to the control unit 60 asinformation. This connection between the pump 40 and the control unit 60is merely illustrated with broken lines in FIG. 9.

In the automatic sample injector shown, it is therefore ensured that thepressure in the sample loop is adjusted to the current operatingpressure of the chromatography column by means of decompression in thesufficiently (high) pressure-resistant sample conveying device when theinjection valve is in a special intermediate position, namely thePRESSURE COMPENSATION position, before the intake segment is moved intothe flow path toward the chromatography column, i.e., before theinjection valve is changed over into the INJECT position.

In addition, the pressure in the sample loop is adjusted to theatmospheric pressure (decompression) in the same intermediate positionof the injection valve, namely the PRESSURE COMPENSATION position, bytaking in an exactly defined additional fluid quantity into the sampleconveying device before the sample loop is separated in order to take ina sample volume from a sample container, i.e., before the injectionvalve is changed over into the LOAD position.

The compression and decompression volumes do not flow through theinjection valve. Consequently, the service life of the (high-pressure)injection valve of the sample injector is only limited by theunavoidable abrasion between the rotor and the stator and, ifapplicable, the abrasive effect, for example, of dirt particles orsample material.

As used herein, whether in the above description or the followingclaims, the terms “comprising,” “including,” “carrying,” “having,”“containing,” “involving,” and the like are to be understood to beopen-ended, that is, to mean including but not limited to. Any use ofordinal terms such as “first,” “second,” “third,” etc., in the claims tomodify a claim element does not by itself connote any priority,precedence, or order of one claim element over another, or the temporalorder in which acts of a method are performed. Rather, unlessspecifically stated otherwise, such ordinal terms are used merely aslabels to distinguish one claim element having a certain name fromanother element having a same name (but for use of the ordinal term).

The above described preferred embodiments are intended to illustrate theprinciples of the invention, but not to limit the scope of theinvention. Various other embodiments and modifications to thesepreferred embodiments may be made by those skilled in the art withoutdeparting from the scope of the present invention.

1. A method of operating a liquid chromatography system, the methodincluding: (a) isolating a sample loop of the liquid chromatographysystem from a high-pressure loop of the liquid chromatography system;(b) performing a pressure compensation operation including one of (i)when isolating the sample loop from the high-pressure loop leaves thesample loop at essentially an operating pressure of a liquidchromatography column, increasing a volume connected in the sample loopto reduce the pressure in the sample loop to essentially ambientpressure, or (ii) when the isolated sample loop is at essentiallyambient pressure preparatory to injecting a sample liquid into thehigh-pressure loop, decreasing the volume connected in the sample loopto increase the pressure in the sample loop to essentially the operatingpressure of the liquid chromatography column; and (c) when the pressurecompensation operation comprises decreasing the volume connected in thesample loop to increase the pressure in the sample loop to essentiallythe operating pressure of the liquid chromatography column, furtherincluding connecting the sample loop to the high-pressure loop so that apump pressure from a high-pressure pump of the liquid chromatographysystem is applied to the sample loop and a sample liquid in the sampleloop is free to flow from the sample loop through a portion of thehigh-pressure loop to the chromatography column.
 2. The method of claim1 further including, after performing step (c) of claim 1 to introducethe sample liquid into the chromatography column: (a) isolating thesample loop from the high-pressure loop once the sample liquid isintroduced into the chromatography column; and (b) increasing the volumeconnected in the sample loop to reduce the pressure in the sample loopto essentially ambient pressure.
 3. The method of claim 1 whereinisolating the sample loop from the high-pressure loop includes placingan injection valve in a PRESSURE COMPENSATION position in which (i)first and second sample loop ports of the injection valve are closed soas to facilitate pressurization of the sample loop, and (ii) first andsecond high-pressure ports of the injection valve are connected so as tooperatively connect the high-pressure pump to the chromatography column.4. The method of claim 1 wherein placing the injection valve in thePRESSURE COMPENSATION position includes rotating a rotor of theinjection valve with respect to a stator of the injection valve.
 5. Themethod of claim 1 wherein the volume connected to the sample loop isdefined by a cavity in which a movable element is slidably mounted, andwherein changing the volume connected to the sample loop includessliding the movable element within the cavity.
 6. The method of claim 5further including measuring the pressure of a fluid in at least one ofthe sample loop or the volume connected to the sample loop with apressure sensor.
 7. The method of claim 5, wherein the movable elementis connected to a drive device which is operable to move the movableelement within the cavity, and further including measuring a forceexerted upon the movable element by the drive device.
 8. A method ofinjecting a sample in a liquid chromatography system, the methodincluding: (a) isolating a sample loop of the liquid chromatographysystem from a high-pressure loop of the liquid chromatography system;(b) placing a sample liquid in the sample loop preparatory to injectingthe sample liquid into the high-pressure loop; (c) with the sampleliquid placed in the sample loop and with the sample loop remainingisolated from the high-pressure loop, performing a pressure compensationoperation in which a volume connected in the sample loop is decreased toraise the pressure in the sample loop from ambient pressure to theoperating pressure of a liquid chromatography column of the liquidchromatography system; and (d) connecting the sample loop to thehigh-pressure loop so that a pump pressure from a high-pressure pump isapplied to the sample loop to cause the sample liquid in the sample loopto flow from the sample loop through a portion of the high-pressure loopto the chromatography column.
 9. The method of claim 8 furtherincluding: (a) isolating the sample loop from the high-pressure loop ofthe liquid chromatography system after the sample liquid has flowed intothe high-pressure loop; and (b) increasing the volume connected in thesample loop to reduce the pressure in the sample loop to ambientpressure.
 10. The method of claim 8 wherein isolating the sample loopfrom the high-pressure loop includes placing an injection valve in aPRESSURE COMPENSATION position in which (i) first and second sample loopports of the injection valve are closed so as to facilitatepressurization of the sample loop, and (ii) first and secondhigh-pressure ports of the injection valve are connected so as tooperatively connect the high-pressure pump to the chromatography column.11. The method of claim 10 wherein placing the injection valve in thePRESSURE COMPENSATION position includes rotating a rotor of theinjection valve with respect to a stator of the injection valve.
 12. Themethod of claim 8 wherein the volume connected to the sample loop isdefined by a cavity in which a movable element is slidably mounted, andwherein decreasing the volume connected to the sample loop includessliding the movable element within the cavity.
 13. The method of claim12 further including measuring the pressure of a fluid in at least oneof the sample loop or the volume connected to the sample loop with apressure sensor.
 14. The method of claim 12 wherein the movable elementis connected to a drive device which is operable to move the movableelement within the cavity, and further including measuring a forceexerted upon the movable element by the drive device.
 15. A method ofpreparing a liquid chromatography system for receiving a sample liquid,the method including: (a) isolating a sample loop of the liquidchromatography system from a high-pressure loop of the liquidchromatography system; and (b) with the sample loop isolated from thehigh-pressure loop and with the pressure in the sample loop remaining atan operating pressure of the liquid chromatography column, performing apressure compensation operation in which a volume connected in thesample loop is increased to reduce the pressure in the sample loop toambient pressure.
 16. The method of claim 15 wherein isolating thesample loop from the high-pressure loop includes placing an injectionvalve in a PRESSURE COMPENSATION position in which (i) first and secondsample loop ports of the injection valve are closed so as to facilitatepressurization of the sample loop, and (ii) first and secondhigh-pressure ports of the injection valve are connected so as tooperatively connect the high-pressure pump of the liquid chromatographysystem to the chromatography column.
 17. The method of claim 16 whereinplacing the injection valve in the PRESSURE COMPENSATION positionincludes rotating a rotor of the injection valve with respect to astator of the injection valve.
 18. The method of claim 15 wherein thevolume connected to the sample loop is defined by a cavity in which amovable element is slidably mounted, and wherein increasing the volumeconnected to the sample loop includes sliding the movable element withinthe cavity.
 19. The method of claim 18 further including measuring thepressure of a fluid in at least one of the sample loop or the volumeconnected to the sample loop with a pressure sensor.
 20. The method ofclaim 18 wherein the movable element is connected to a drive devicewhich is operable to move the movable element within the cavity, andfurther including measuring a force exerted upon the movable element bythe drive device.